Chapel Hill, NC So much of what happens inside cells to preserve health or cause disease is so small or time-sensitive that researchers are just now getting glimpses of the complexities unfolding in us every minute of the day.
UNC School of Medicine researchers have discovered one such complexity a previously hidden mode of RNA regulation vital for bacterial defence against toxic fluoride ions.
Published in the journal Nature Chemical Biology, the discovery opens a new research avenue for developing drugs that target RNA genetic molecules important for various biological processes, including how genes are regulated.
Much research to find the underpinnings of health and disease has rightfully focused on proteins, but different forms of RNA have functions were just beginning to understand, said Dr.Qi Zhang, senior author and assistant professor of biochemistry and biophysics. Our NMR technique is helping us learn more than ever before.
In 2014, Zhang and colleagues developed a new way to use nuclear magnetic resonance (NMR) imaging to show the shape and motion of RNA at the atomic level over time. This was crucial because RNA is often short-lived and sparsely populated in cells at any given time. The amount of RNA changes over short bursts of time depending on which one of its various roles it is fulfilling. Yet, until now, structural biologists have only visualized RNA as a series of snapshots. Zhangs technique enables new ways of visualizing RNA, down to its atoms.
We need this atomic level view because every atomic interaction is important to human health, said Zhang, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Scientists have developed similar approaches that work well for proteins and we needed this for RNA, which is crucial for understanding how an RNA serves as a control switch for gene expression.
In their latest work, Zhang and colleagues studied riboswitches a class of noncoding RNAs that are not translated from DNA into proteins. Rather, riboswitches control gene expression in response to specific cellular cues. Many bacteria rely on these cues and controls to regulate fundamental cellular function. These switches have been important models for the scientific communitys basic understanding of RNA architecture and ligands molecules such as drug compounds. Riboswitches have emerged as targets for a new class of very much needed antibacterial drugs.
Heres the prevailing wisdom of how these riboswitches work: when a cell produces a metabolite or encounters a toxin to a certain level, a sensor on the riboswitch detects this, reshapes the switchs three-dimensional structure, and sends a signal to turn the responsible gene circuit on or off. This model has been shown in a...